Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells

It is unclear whether the abnormal relaxation seen in diabetes is due to decreased levels of nitric oxide (NO) and how eicosapentaenoic acid (EPA, C20:5 omega 3) affects the endothelial production of NO. We investigated the effects of EPA ethyl ester (EPA-E) and elevated glucose on NO production by human endothelial cells (HUE), EPA-E (0.3 mM) significantly enhanced [NO2-] production and the intracellular concentration of free Ca2+ within 3 min after EPA-E was added to the cultures. High levels of glucose (27.5 mM) significantly increased endothelial glucose, sorbitol and fructose, and inhibited [NO2-] production, However, EPA-E (0.3 mM) prevented the inhibition of [NO2-] production due to the activation of the Ca2+-calmodulin system of NO synthase, EPA-E decreased the glucose mediated inhibition of NO production by HUE. These results suggest this agent might ameliorate endothelial dysfunction associated with diabetes. (C) 1997 Academic Press.